Crystal structure of bis­{2-[amino(iminium­yl)meth­yl]-1,1-di­methyl­guanidine} carbonate methanol disolvate

Dong, J.; Liu, B.; Yang, B.

doi:10.1107/S2056989015016771

organic compounds

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ISSN: 2056-9890

Volume 71| Part 10| October 2015| Pages o747-o748

doi:10.1107/S2056989015016771

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Crystal structure of bis{2-[amino(iminiumyl)methyl]-1,1-dimethylguanidine} carbonate methanol disolvate

Jinlong Dong,^a Bin Liu ^a and Binsheng Yang ^a ^*

^aInstitute of Molecular Science, Key Laboratory of Chemical Biology of Molecular Engineering of Education Ministry, Shanxi University, Taiyuan 030006, People's Republic of China
^*Correspondence e-mail: dongjinlong20123@163.com

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 2 September 2015; accepted 8 September 2015; online 12 September 2015)

In the title solvated molecular salt, 2C₄H₁₂N₅⁺·CO₃²⁻·2CH₃OH, the complete carbonate ion is generated by crystallographic twofold symmetry, with the C atom and one O atom lying on the rotation axis. The cation is twisted about the central C—N bond [C—N—C—N = −137.7 (6)°]. In the crystal, the components are linked by N—H⋯O, N—H⋯N and O—H⋯O hydrogen bonds, generating a three-dimensional supramolecular network.

Keywords: crystal structure; metformin; sodium carbonate; hydrogen bonding.

CCDC reference: 1422939

1. Related literature

For background to and medical applications of metformin (systematic name: N,N-dimethylimidodicarbonimidic diamide), see: Castagnolo et al. (2011 ); De Jager et al. (2005 ); Pérez-Fernández et al. (2013 ); Yardımcı & Özaltın (2005 ); Xi et al. (2008 ); Li et al. (2005 ). For a related structure, see: Huang et al. (2008 ).

2. Experimental

2.1. Crystal data

2C₄H₁₂N₅⁺·CO₃²⁻·2CH₄O
M_r = 384.46
Monoclinic, C 2/c
a = 13.5726 (12) Å
b = 10.5634 (8) Å
c = 13.9825 (13) Å
β = 90.386 (1)°
V = 2004.7 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 298 K
0.40 × 0.32 × 0.29 mm

2.2. Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2000 ) T_min = 0.961, T_max = 0.971
4837 measured reflections
1749 independent reflections
947 reflections with I > 2σ(I)
R_int = 0.065

2.3. Refinement

R[F² > 2σ(F²)] = 0.083
wR(F²) = 0.280
S = 1.02
1749 reflections
123 parameters
6 restraints
H-atom parameters constrained
Δρ_max = 0.64 e Å⁻³
Δρ_min = −0.29 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O1ⁱ	0.86	2.04	2.883 (5)	166
N1—H1B⋯N3ⁱⁱ	0.86	2.21	3.069 (6)	175
N2—H2A⋯O1ⁱⁱⁱ	0.86	1.96	2.818 (5)	178
N2—H2B⋯O3^iv	0.86	2.08	2.896 (6)	159
N5—H5A⋯O1^iv	0.86	1.95	2.728 (4)	150
O3—H3⋯O2	0.82	1.77	2.591 (5)	177
Symmetry codes: (i) $[-x+{\script{3\over 2}}, -y+{\script{3\over 2}}, -z+1]$ ; (ii) -x+2, -y+1, -z+1; (iii) $[x+{\script{1\over 2}}, -y+{\script{3\over 2}}, z-{\script{1\over 2}}]$ ; (iv) -x+1, -y+1, -z+1.

Data collection: APEX2 (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

CCDC reference: 1422939

Crystal structure: contains datablock I. DOI: 10.1107/S2056989015016771/hb7495sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S2056989015016771/hb7495Isup2.hkl

Supporting information file. DOI: 10.1107/S2056989015016771/hb7495Isup3.cml

checkCIF report

Structural commentary top

Metformin, an oral antidiabetic drug, has been extensively used throughout the world over the last five decades to treat type-2 diabetes mellitus[Castagnolo et al. , 2011; De Jager et al. , 2005; Pérez-Fernández et al. , 2013 ], in particular, in overweight and obese people. Metformin has a distinct advantage of lowering serum glucose levels without causing hyper-insulinemia and subsequent risk of hypoglycemia [Yardimci et al. , 2005; Xi et al. , 2008; Liu et al. , 2005]. In order to find a substance that enhances the therapeutic effects of metformin, and exhibits additional pancreas-protecting effects, we synthesized the title compound (Fig. 1). Some examples of related structures already appear in the literature[Pérez-Fernández et al. , 2013; Huamg et al. , 2008]. The structure of the title compound contains two metformin molecules, one methanol molecule and carbonate ion (Fig. 1). In the crystal, N—H···O, N—H···N and O—H···O hydrogen bonds connect molecules to form a two-dimensional network parallel to (001) (Fig. 2).

Refinement details top

Crystal data, data collection and structure refinement details are summarized in Table 1.The N—H hydrogen atom was located in a difference Fourier map and freely refined: N—H = 0.86 Å. The C-bound H-atoms were included in calculated positions and treated as riding atoms: C—H = 0.96 Å with U_iso (H) = 1.2 or 1.5U_eq (C).

Synthesis and crystallization top

A methanol solution (20 ml) of sodium carbonate (485 mg, 3.03 mmol) and metformin hydrochloride (500 mg, 3.03 mmol) was stirred for 12 h at room temperature. The solid part (sodium chloride) was filtered off. The rest of the solution was slowly evaporated at room temperature, yielding colourless blocks of the title compound.

Related literature top

For background to and medical applications of metformin (systematic name: N,N-dimethylimidodicarbonimidic diamide), see: Castagnolo et al. (2011); De Jager et al. (2005); Pérez-Fernández et al. (2013); Yardımcı & Özaltın (2005); Xi et al. (2008); Li et al. (2005). For a related structure, see: Huang et al. (2008). .

Computing details top

Data collection: APEX2 (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of the title compound with displacement ellipsoids drawn at the 30% probability level.
	Fig. 2. Part of the crystal structure with the hydrogen bonds drawn as dashed lines.

Bis{2-[amino(iminiumyl)methyl]-1,1-dimethylguanidine} carbonate methanol disolvate top

Crystal data top

2C₄H₁₂N₅⁺·CO₃²⁻·2CH₄O	F(000) = 832
M_r = 384.46	D_x = 1.274 Mg m⁻³
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 13.5726 (12) Å	Cell parameters from 1052 reflections
b = 10.5634 (8) Å	θ = 2.8–22.8°
c = 13.9825 (13) Å	µ = 0.10 mm⁻¹
β = 90.386 (1)°	T = 298 K
V = 2004.7 (3) Å³	Block, colourless
Z = 4	0.40 × 0.32 × 0.29 mm

Data collection top

Bruker APEXII CCD diffractometer	947 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.065
φ and ω scans	θ_max = 25.1°, θ_min = 2.8°
Absorption correction: multi-scan (SADABS; Bruker, 2000)	h = −16→15
T_min = 0.961, T_max = 0.971	k = −12→11
4837 measured reflections	l = −16→16
1749 independent reflections

Refinement top

Refinement on F²	6 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.083	H-atom parameters constrained
wR(F²) = 0.280	w = 1/[σ²(F_o²) + (0.1395P)² + 3.7847P] where P = (F_o² + 2F_c²)/3
S = 1.02	(Δ/σ)_max < 0.001
1749 reflections	Δρ_max = 0.64 e Å⁻³
123 parameters	Δρ_min = −0.29 e Å⁻³

Crystal data top

2C₄H₁₂N₅⁺·CO₃²⁻·2CH₄O	V = 2004.7 (3) Å³
M_r = 384.46	Z = 4
Monoclinic, C2/c	Mo Kα radiation
a = 13.5726 (12) Å	µ = 0.10 mm⁻¹
b = 10.5634 (8) Å	T = 298 K
c = 13.9825 (13) Å	0.40 × 0.32 × 0.29 mm
β = 90.386 (1)°

Data collection top

Bruker APEXII CCD diffractometer	1749 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2000)	947 reflections with I > 2σ(I)
T_min = 0.961, T_max = 0.971	R_int = 0.065
4837 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.083	6 restraints
wR(F²) = 0.280	H-atom parameters constrained
S = 1.02	Δρ_max = 0.64 e Å⁻³
1749 reflections	Δρ_min = −0.29 e Å⁻³
123 parameters

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
N1	0.9937 (3)	0.6120 (4)	0.3964 (3)	0.0764 (14)
H1A	1.0180	0.6664	0.3574	0.092*
H1B	1.0312	0.5752	0.4377	0.092*
N2	0.8445 (3)	0.6436 (4)	0.3289 (3)	0.0651 (12)
H2A	0.8709	0.6975	0.2908	0.078*
H2B	0.7824	0.6279	0.3250	0.078*
N3	0.8641 (3)	0.5040 (4)	0.4562 (3)	0.0753 (14)
N4	0.7163 (3)	0.4414 (5)	0.5183 (3)	0.0787 (14)
N5	0.7482 (3)	0.3984 (4)	0.3619 (3)	0.0663 (12)
H5A	0.6934	0.3578	0.3579	0.080*
H5B	0.7857	0.4044	0.3128	0.080*
O1	0.43093 (19)	0.6744 (3)	0.7084 (2)	0.0513 (9)
O2	0.5000	0.4941 (4)	0.7500	0.0802 (17)
O3	0.3680 (3)	0.3385 (6)	0.6850 (5)	0.143 (2)
H3	0.4110	0.3854	0.7063	0.214*
C1	0.8990 (3)	0.5850 (5)	0.3931 (3)	0.0584 (12)
C2	0.7748 (3)	0.4516 (5)	0.4435 (3)	0.0627 (14)
C3	0.6269 (4)	0.3681 (7)	0.5153 (4)	0.095 (2)
H3A	0.5800	0.4085	0.4737	0.143*
H3B	0.6001	0.3621	0.5785	0.143*
H3C	0.6410	0.2847	0.4917	0.143*
C4	0.7393 (6)	0.5018 (9)	0.6077 (5)	0.127 (3)
H4A	0.8000	0.5476	0.6020	0.191*
H4B	0.7458	0.4389	0.6568	0.191*
H4C	0.6873	0.5594	0.6240	0.191*
C5	0.3996 (9)	0.2845 (15)	0.6049 (14)	0.279 (10)
H5D	0.3442	0.2644	0.5646	0.419*
H5E	0.4349	0.2084	0.6203	0.419*
H5F	0.4424	0.3419	0.5719	0.419*
C6	0.5000	0.6130 (5)	0.7500	0.0422 (13)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.055 (2)	0.092 (3)	0.082 (3)	−0.035 (2)	−0.022 (2)	0.034 (2)
N2	0.050 (2)	0.079 (3)	0.067 (3)	−0.0205 (19)	−0.0089 (19)	0.017 (2)
N3	0.065 (3)	0.104 (3)	0.056 (2)	−0.049 (2)	−0.0220 (19)	0.023 (2)
N4	0.076 (3)	0.108 (4)	0.051 (3)	−0.041 (3)	0.000 (2)	−0.003 (2)
N5	0.058 (2)	0.093 (3)	0.047 (2)	−0.034 (2)	−0.0063 (17)	0.000 (2)
O1	0.0389 (15)	0.0469 (17)	0.068 (2)	−0.0007 (12)	−0.0176 (13)	−0.0020 (14)
O2	0.060 (3)	0.037 (3)	0.144 (5)	0.000	−0.032 (3)	0.000
O3	0.063 (3)	0.135 (4)	0.230 (7)	−0.016 (3)	0.011 (3)	−0.097 (4)
C1	0.051 (3)	0.076 (3)	0.048 (2)	−0.024 (2)	−0.009 (2)	0.006 (2)
C2	0.059 (3)	0.079 (3)	0.050 (3)	−0.032 (2)	−0.012 (2)	0.015 (2)
C3	0.076 (4)	0.133 (5)	0.077 (4)	−0.048 (4)	0.007 (3)	0.010 (4)
C4	0.140 (6)	0.180 (8)	0.062 (4)	−0.046 (6)	0.006 (4)	−0.028 (5)
C5	0.153 (9)	0.254 (15)	0.43 (2)	−0.090 (10)	0.122 (12)	−0.223 (16)
C6	0.029 (3)	0.039 (3)	0.059 (4)	0.000	−0.007 (2)	0.000

Geometric parameters (Å, º) top

N1—C1	1.317 (6)	C6—O1	1.276 (4)
N1—H1A	0.8600	C6—O2	1.257 (7)
N1—H1B	0.8600	O3—C5	1.330 (13)
N2—C1	1.314 (6)	O3—H3	0.8200
N2—H2A	0.8600	C3—H3A	0.9600
N2—H2B	0.8600	C3—H3B	0.9600
N3—C1	1.319 (6)	C3—H3C	0.9600
N3—C2	1.344 (5)	C4—H4A	0.9600
N4—C2	1.321 (6)	C4—H4B	0.9600
N4—C4	1.436 (8)	C4—H4C	0.9600
N4—C3	1.440 (6)	C5—H5D	0.9600
N5—C2	1.320 (6)	C5—H5E	0.9600
N5—H5A	0.8600	C5—H5F	0.9600
N5—H5B	0.8600	C6—O1ⁱ	1.276 (4)

C1—N1—H1A	120.0	N4—C3—H3B	109.5
C1—N1—H1B	120.0	H3A—C3—H3B	109.5
H1A—N1—H1B	120.0	N4—C3—H3C	109.5
C1—N2—H2A	120.0	H3A—C3—H3C	109.5
C1—N2—H2B	120.0	H3B—C3—H3C	109.5
H2A—N2—H2B	120.0	N4—C4—H4A	109.5
C1—N3—C2	120.4 (4)	N4—C4—H4B	109.5
C2—N4—C4	121.7 (5)	H4A—C4—H4B	109.5
C2—N4—C3	122.1 (4)	N4—C4—H4C	109.5
C4—N4—C3	116.2 (5)	H4A—C4—H4C	109.5
C2—N5—H5A	120.0	H4B—C4—H4C	109.5
C2—N5—H5B	120.0	O3—C5—H5D	109.5
H5A—N5—H5B	120.0	O3—C5—H5E	109.5
C5—O3—H3	109.5	H5D—C5—H5E	109.5
N2—C1—N1	117.9 (4)	O3—C5—H5F	109.5
N2—C1—N3	124.0 (4)	H5D—C5—H5F	109.5
N1—C1—N3	118.1 (4)	H5E—C5—H5F	109.5
N5—C2—N4	119.2 (4)	O2—C6—O1ⁱ	120.5 (2)
N5—C2—N3	122.0 (4)	O2—C6—O1	120.5 (2)
N4—C2—N3	118.4 (4)	O1ⁱ—C6—O1	119.0 (5)
N4—C3—H3A	109.5

C2—N3—C1—N2	17.2 (8)	C4—N4—C2—N3	9.8 (9)
C2—N3—C1—N1	−165.0 (5)	C3—N4—C2—N3	−169.3 (6)
C4—N4—C2—N5	−177.3 (7)	C1—N3—C2—N5	49.6 (8)
C3—N4—C2—N5	3.6 (9)	C1—N3—C2—N4	−137.7 (6)

Symmetry code: (i) −x+1, y, −z+3/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1ⁱⁱ	0.86	2.04	2.883 (5)	166
N1—H1B···N3ⁱⁱⁱ	0.86	2.21	3.069 (6)	175
N2—H2A···O1^iv	0.86	1.96	2.818 (5)	178
N2—H2B···O3^v	0.86	2.08	2.896 (6)	159
N5—H5A···O1^v	0.86	1.95	2.728 (4)	150
O3—H3···O2	0.82	1.77	2.591 (5)	177

Symmetry codes: (ii) −x+3/2, −y+3/2, −z+1; (iii) −x+2, −y+1, −z+1; (iv) x+1/2, −y+3/2, z−1/2; (v) −x+1, −y+1, −z+1.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1ⁱ	0.86	2.04	2.883 (5)	166
N1—H1B···N3ⁱⁱ	0.86	2.21	3.069 (6)	175
N2—H2A···O1ⁱⁱⁱ	0.86	1.96	2.818 (5)	178
N2—H2B···O3^iv	0.86	2.08	2.896 (6)	159
N5—H5A···O1^iv	0.86	1.95	2.728 (4)	150
O3—H3···O2	0.82	1.77	2.591 (5)	177

Symmetry codes: (i) −x+3/2, −y+3/2, −z+1; (ii) −x+2, −y+1, −z+1; (iii) x+1/2, −y+3/2, z−1/2; (iv) −x+1, −y+1, −z+1.

Acknowledgements

We are very grateful for financial support from the National Natural Science Foundation of PR China (Nos. 21271122 and 21571117) and a Research Project Supported by Shanxi Scholarship Council of China (2013–018).

References

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CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 71| Part 10| October 2015| Pages o747-o748

doi:10.1107/S2056989015016771

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Crystal structure of bis­­{2-[amino(iminium­yl)meth­yl]-1,1-di­methyl­guanidine} carbonate methanol disolvate

1. Related literature

2. Experimental

2.1. Crystal data

2.2. Data collection

2.3. Refinement

Supporting information

Acknowledgements

References

organic compounds

Crystal structure of bis{2-[amino(iminiumyl)methyl]-1,1-dimethylguanidine} carbonate methanol disolvate